Innate lymphocytes such as NK, invariant natural killer T (iNKT) cells and γδ T cells mount rapid effector responses and therefore are important sentinels of the innate immune system and until recently were thought to be short-lived. Memory type NK cells have been identified and intensively studied in several systems (non-patent documents 1-4). In murine cytomegalovirus (MCMV) infection, Ly49H+ NK cells have been found to be long-lived and to have a role in shaping prolonged anti-viral-specific NK cell responses and also to possess “memory” of previously encountered pathogens. Results of a global transcriptional analysis in the immunological genome project showed common memory transcripts and some shared markers of NK cells and CD8+ T cells, suggesting conservation between the NK cell and CD8+ T cell lineages of some activation mechanisms (non-patent document 5). In addition, memory γδT cells capable of simultaneously producing IFN-γ and IL-17 in the intestinal tissues have recently been identified (non-patent document 6).
iNKT cells express an invariant T cell antigen receptor (TCR) α-chain that is the product of a canonical rearrangement between the Vα14 (Vα24 in human) and the Jα18 gene segments, with a CDR3α region that is invariant at the amino acid level. These iNKT cells recognize a complex of the antigen-presenting MHC-like molecule CD1d and a glycolipid and secrete cytokines in an antigen-specific manner following engagement of their TCR (non-patent documents 7-10). The synthetic iNKT ligand (also referred to as iNKT ligand or CD1d ligand), α-galactosylceramide (α-GalCer) can be loaded (or “pulsed”) onto CD1d-expressing cells such as, in addition to dendritic cells (DCs), CD1d-transfected tumor cells and fibroblasts (non-patent documents 11-13). By α-GalCer loaded CD1d-positive cells (CD1d+ cells), iNKT cells are activated and capable of producing large quantities of interferon-γ (IFN-γ) (non-patent documents 11-13).
Immunotherapies utilizing the activation of iNKT cells (iNKT cell activation therapy) have heretofore been developed. One of them is a method aiming at functional recovery of the iNKT cells in the body of patients, which includes growing iNKT cells obtained from the patients in vitro and returning them to the body. Another method aiming at activation of iNKT cells by loading dendritic cell (DC) collected from the peripheral blood of patient with α-GalCer (DC/Gal) and returning same to the body of the patients has been developed and is also called a dendritic cell therapy. The safety and effect of this method has been verified by clinical tests (non-patent documents 14-17).
In addition, a new cell preparation for immunity induction using CD1d-positive cells, which causes activation of iNKT cells and maturation of DCs has been developed (patent document 1).